Inhibition of arachidonic acid cyclo-oxygenase and lipoxygenase activities of leukocytes by indomethacin and compound BW755C.
Arachidonic acid is metabolized via two pathways in leukocytes: cyclo-oxygenase, leading to the stable prostaglandins, and lipoxygenase, leading to hydroxyacids. Indomethacin inhibits the cyclo-oxygenase selectively, whereas compound BW755C (3-amino-1-(m-(trifluoromethyl)phenyl)-2-pyrazoline) inhibits both pathways equally. This offers a possible explanation for the differing activities of these two compounds in inflammatory models in vivo. The patterns of product inhibition by the two compounds support the suggestion that 11-HETE (hydroxy-eicosate-traenoic acid) and 15-HETE can arise by incomplete operation of the cyclo-oxygenase pathway.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000096:biosynthesis / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors; D007213:Indomethacin / Q000494:pharmacology*; D007962:Leukocytes / Q000201:enzymology*; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles / Q000494:pharmacology*; D011817:Rabbits
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D007213:Indomethacin